The physiological function and the mode of regulation of transglutaminases are being studied as to their role in the formation of temporary tissue matrix (fibrinconnective tissue matrix) during tissue or bone fracture repair and in the modulation of specific cellular processes. The physiological significance and biochemical mechanism of factor XIIIa (plasma transglutaminase) and tissue transglutaminase catalyzed cross-linking of plasmin inhibitor (Alpha2PI) to fibrin and other matrix proteins are under investigation both in vivo and in vitro. The cross-linking of Alpha2PI to fibrin plays a major role in stabilization of a temporary matrix which is vital for the initial phase of cell migration and proliferation at wound sites. A number of factors in the plasma and tissue fluid can effect the fibrin stabilization, i.e., glutathione, superoxides, and metal ions. We now find albumin plays an important role in the modulation of both fibrin gel-formation and stabilization. Factor XIII (a2) has been isolated from human uterus and placenta but its origin is not known. By immunohistological methods, the increased level of Factor XIII (a2) antigen was observed in the myometrium and endometrium of the pregnant rabbit uterus and a concomitant increase of thrombin-dependent transglutaminase activity was also detected in the same tissues. In cells activated by mitogens and transformed cells, various molecular forms of transglutaminase have been identified. In the lung and muscle, most of enzyme activities are associated with non-extractable insoluble matrix proteins whereas in the liver and kidney, the majority of enzyme activity is found in the cytosol fractions. The intrinsic substrates for the extracellular matrix-bound enzymes are also localized in the same proteins.